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Background RAS mutation status is considered a powerful prognostic factor in patients undergoing hepatectomy for colorectal liver metastases (CLM). However, whether its prognostic power is robust regardless of administration of preoperative chemotherapy or tumor burden remains unclear. Methods Consecutive patients who underwent initial hepatectomy for CLM from April 2010 through March 2017 in two hospitals were included. The prognostic value of KRAS was compared based on whether patients received preoperative chemotherapy and their tumor burden score (TBS). Results We included 409 patients (median follow-up 38 months). In the preoperative chemotherapy group, patients with mutant KRAS (mt-KRAS) CLM had poorer overall survival (OS) than those with wild KRAS (wt-KRAS; 5-year OS: 37.7% vs 53.8%, p = 0.024), although their OS was not different from patients undergoing upfront surgery. Similarly, patients with mt-KRAS had poorer OS than those with wt-KRAS in TBS of 3-9 (5-year OS: 33.1% vs 63.2%, p = 0.001), although their OS was not different from patients with TBS 3 or ≥ 9. Conclusions In patients undergoing hepatectomy for CLM, the prognostic value of KRAS depends on their history of preoperative chemotherapy or tumor burden.

Purpose Neoadjuvant chemotherapy (NACT) is increasingly adopted in the therapy of breast cancer (BC) patients with positive axillary nodes (cN+), but the reliability and feasibility of sentinel lymph node biopsy (SLNB) following NACT are still controversial. The objective of the present study is to conduct an updated meta-analysis on this issue. Methods A literature search was performed using PubMed, Cochrane, Embase, and Web of Science to identify papers published from January 1, 2000 to October 22, 2020 to research SLNB after NACT in BC patients. Studies that met the quality standard were enrolled for this meta-analysis. Results A total of 3578 participants from 27 trials were included in this meta-analysis. The pooled estimate of the identification rate (IR) for SLNB was 91 %, and the false negative rate (FNR) was 15 %. The pooled negative prediction value (NPV), accuracy, specificity, and sensitivity were 82 %, 89 %, 97 %, and 85 %, respectively. In subgroup analysis, the application of dual mapping could clearly decrease the FNR. The FNR was significantly high in the luminal types, and it declined as more sentinel lymph nodes (SLNs) were removed. Conclusion SLNB following NACT is now technically feasible for BC with cN+. However, it must be emphasized that the FNR is unacceptable high., Highlights • We performed a meta-analysis to provide a consensus regarding the application of SLNB post-NACT in cN + patients. • One comprehensive database search yielded 27 studies (3578 patients). • The pooled estimate of IR for SLNB was 91 %, and FNR was 15 %. • The application of dual mapping could clearly decrease the FNR.

Background: Evaluating the tumor response to neoadjuvant chemotherapy is key to planning further therapy of breast cancer. Our study aimed to evaluate the effectiveness of low-energy and subtraction contrast-enhanced spectral mammography (CESM) images in the detection of complete response (CR) for neoadjuvant chemotherapy (NAC) in breast cancer. Methods: A total of 63 female patients were qualified for our retrospective analysis. Low-energy and subtraction CESM images just before the beginning of NAC and as a follow-up examination 2 weeks before the end of chemotherapy were compared with one another and assessed for compliance with the postoperative histopathological examination (HP). The response to preoperative chemotherapy was evaluated based on the RECIST 1.1 criteria (Response Evaluation Criteria in Solid Tumors). Results: Low-energy images tend to overestimate residual lesions (6.28 mm) and subtraction images tend to underestimate them (2.75 mm). The sensitivity of low-energy images in forecasting CR amounted to 33.33%, while the specificity was 92.86%. In the case of subtraction CESM, the sensitivity amounted to 85.71% and the specificity to 71.42%. Conclusions: CESM is characterized by high sensitivity in the assessment of CR after NAC. The use of only morphological assessment is insufficient. CESM correlates well with the size of residual lesions on histopathological examination but tends to underestimate the dimensions.

Introduction: Wilms’ tumour is the most common childhood renal malignancy, with 5–10% of cases presenting bilaterally 1. However, there is currently no consensus between centres on optimal management of bilateral Wilms’ tumours. This is an international multi-centre case series comparing management and outcomes of bilateral Wilms’ tumours between low-income centres (LIC) and high-income centres (HIC). Methods: Patients with bilateral Wilms' tumour were identified from four tertiary referral centres internationally. Data were collected on baseline characteristics, disease status, treatment used and clinical outcomes. Results were compared between individual centres as well as between groups of low-income centres (LIC) and high-income centres (HIC). Results: Data were collected for forty patients. Most patients received preoperative chemotherapy ( n = 38, 95%). The most common surgical procedures were bilateral nephron-sparing surgery ( n = 10, 25%) and nephrectomy with partial nephrectomy ( n = 20, 50%). Ten-year survival after treatment was as follows: LIC's n = 13 (65%); HIC's n = 20 (100%) ( p = 0.01). Discussion: Ten-year survival was significantly higher in HIC's. Our results show this may be caused by patient factors such as later presentation with more advanced disease in low-income centres. This comparative case series is the first to report on a large number of cases from multiple international centres, and to compare key outcomes.

Background Sinusoidal obstruction syndrome (SOS) due to chemotherapy can cause severe hepatotoxicity, leading to impaired outcome in patients with colorectal cancer. A previous study introduced gadoxetic acid-enhanced magnetic resonance imaging (Gd-EOB-MRI) to diagnose SOS. Purpose To assess the reproducibility of Gd-EOB-MRI-based SOS diagnosis and its relationship with response to chemotherapy and long-term outcome. Material and Methods Twenty-six Gd-EOB-MRI scans of patients undergoing chemotherapy for colorectal liver metastases (CRLM) were retrospectively analyzed. Three radiologists, blinded to clinical data, independently scored presence and severity of SOS on a 5-point scale (0, definitely not present to 4, definitely present). Patients with a score ≥3 were considered SOS+. Inter-observer agreement between readers was assessed with kappa statistics. Response (RECIST 1.1.), occurrence of new CRLM during follow-up (hepatic progression) and overall survival (OS) were compared between patients with and without SOS. Results The inter-observer agreement of SOS scores was poor, with quadratic kappas of 0.17–0.40. For the binary outcome of SOS+ (confidence level [CL] 3–4) vs. SOS– (CL 0–2) agreement was poor, with kappas of 0.03–0.37. Median follow-up was 24 months (range 4–44 months). Response and OS between patients with and without SOS did not differ significantly for any of the readers. Conclusion Inter-observer agreement for the diagnosis of SOS on Gd-EOB-MRI is poor. No significant correlation with relevant outcomes was found for any of the readers. Therefore, MRI for SOS diagnosis might be less useful than previously reported. Other techniques should be explored to accurately diagnose SOS in absence of histological confirmation.

Qingshan Huang,1,2 Chenglong Chen,1,2 Jingbing Lou,1,2 Yi Huang,1,2 Tingting Ren,1,2 Wei Guo1,2 1Musculoskeletal Tumor Center, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Beijing Key Laboratory of Musculoskeletal Tumor, Peking University People’s Hospital, Beijing, People’s Republic of ChinaCorrespondence: Wei GuoMusculoskeletal Tumor Center, Peking University People’s Hospital, Beijing, 100044, People’s Republic of ChinaTel/Fax +86-10-88324471Email bonettumor@163.comBackground: Due to the obvious heterogeneity of osteosarcoma, many patients are not sensitive to neoadjuvant chemotherapy. In this study, the clinical characteristics and auxiliary examinations of patients with osteosarcoma were used to predict the effect of preoperative chemotherapy, so as to guide the clinical adjustment of the treatment plan to improve the prognosis of patients.Methods: In this study, 90 patients with pathologically confirmed osteosarcoma were included, and they were randomly divided into training cohort (n=45) and validation cohort (n=45). A prediction model of preoperative chemotherapy efficacy for osteosarcoma was established by multivariate logistic regression analysis, and a nomogram was used as the visualization of the model. The ROC curve and C-index were used to evaluate the accuracy of the nomogram. Decision curve analysis (DCA) was used to evaluate the net benefit of the nomogram in predicting the efficacy of neoadjuvant chemotherapy under different threshold probabilities.Results: In the study, the age, gender, location, tumor volume, metastasis at the first visit, MSTS staging, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) were used in the multivariate logistic regression analysis and the construction of the nomogram. The AUC and C-index of the training cohort were 0.793 (95% CI: 0.632, 0.954) and 0.881 (95% CI: 0.776, 0.986), respectively. The AUC and C-index in the validation cohort were 0.791 (95% CI: 0.644, 0.938) and 0.813 (95% CI: 0.679, 0.947), respectively, which were close to the training cohort. DCA showed that the model had good clinical application value.Conclusion: Based on the clinical characteristics of patients and auxiliary examinations, the nomogram can be good used to predict the efficacy of preoperative chemotherapy for osteosarcoma.Keywords: osteosarcoma, nomogram, chemotherapy, ROC, necrosis rate

Summary Background The effects of cytotoxic chemotherapy on the expression of programmed death ligand 2 (PD-L2) are unknown and little is known about how the tumor microenvironment changes following neoadjuvant chemotherapy in locally advanced gastroesophageal adenocarcinomas (AEG). Recently, a number of studies reported that cytotoxic chemotherapy affects the expression levels of programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1). Regarding PD-L2, the second known ligand of PD‑1, no data on potential changes in expression patterns in patients with preoperatively treated AEG are available. The aim of this study was to investigate the impact of cytotoxic chemotherapy on PD-L2 expression in patients with resectable AEG. Methods Consecutive patients with locally advanced AEG treated with preoperative cytotoxic chemotherapy were included. PD-L2 expression by cancer cells (CCs) and tumor-infiltrating lymphocytes (TILs) was investigated in samples of paired diagnostic biopsies and resected tumor specimens by immunohistochemistry using two different anti-PD-L2 antibodies. Results Included were 40 patients with AEG and available paired tumor tissue samples. PD-L2 expression was observed in one diagnostic biopsy sample by CCs and in one diagnostic biopsy sample by TILs. There was no difference concerning the expression levels measured by the two antibodies. Conclusion In contrast to previously published studies reporting PD-L2 expression rates of up to 50% in AEGs, in our cohort, PD-L2 expression seems to play no significant role in AEG.

Neoadjuvant systemic therapy has many potential advantages over up-front surgery, including tumor downstaging, early treatment of micrometastatic disease, and providing an in vivo test of tumor biology. Due to these advantages, neoadjuvant therapy is becoming the standard of care for an increasing number of tumor types. Currently, colon cancer patients are still routinely treated with up-front surgery, and neoadjuvant systemic therapy is not yet standard. Limitations to widespread use of neoadjuvant therapy have included inaccurate radiological staging, concerns about tumor progression while undergoing preoperative treatment rendering a patient incurable, and a lack of randomized data demonstrating benefit. However, there is great interest in neoadjuvant chemotherapy, and a number of trials are under way. Early follow up of the first phase III trial of neoadjuvant chemotherapy for colon cancer demonstrated tumor downstaging and suggested an improvement in disease-free survival with neoadjuvant chemotherapy, and it is hoped that this will translate into longer-term overall survival benefit. Clinicians should closely watch this developing field, consider the option of neoadjuvant chemotherapy for colon cancer patients, and actively seek out opportunities for their patients to participate in ongoing clinical trials to further inform this field in future.

Background/aim This study aimed to evaluate how NAD(P)H: quinone oxidoreductase-1 (NQO1) affects survival after hepatectomy in patients with colorectal liver metastasis (CRLM). Patients and methods A retrospective analysis was conducted of 88 consecutive patients who underwent hepatectomy for CRLM. Of the 88 patients, preoperative chemotherapy was administered to 30 patients. Immunohistochemistry of the resected specimens was conducted using monoclonal anti-NQO1 antibody. Results NQO1-positive expression in tumor cells of CRLM was associated with worse overall survival (p=0.026) and was an independent adverse prognostic factor in multivariate analysis (hazard ratio=5.296, p=0.007). Among 30 patients who received preoperative chemotherapy, patients with loss of NQO1 expression in non-neoplastic epithelial cells of the bile ducts (NQO1 polymorphism: n=19) showed significantly better response to preoperative chemotherapy for CRLM (p=0.004). Conclusion NQO1-positive expression in tumor cells of CRLM may be an adverse prognostic factor after hepatectomy for CRLM.

Objective To perform a meta-analysis to determine the effect of loco-regional radiation therapy (RT) compared to no loco-regional RT for operated patients in clinical stage cN2 breast cancer at diagnosis and ypN0 after preoperative chemotherapy (PST). Material and Methods Eligible studies were identified through a systematic search of the medical literature performed independently by two researchers using a validated search strategy. An electronic search of Medline via PubMed and Embase (Breast cancer AND preoperative chemotherapy AND radiation therapy) was conducted with no language or publication status restrictions. The effect of loco-regional RT on overall (OS), disease free (DFS), loco-regional recurrence-free (LRRFS) survival and local recurrence was evaluated. An electronic search of Medline via PubMed and Embase (Toxicity AND radiation therapy breast cancer AND preoperative therapy; toxicity AND breast surgery AND preoperative chemotherapy) was conducted for outcomes of harm: major acute and late skin toxicity, lymphedema and cardiac events. Results Of 333 studies identified, 4 retrospective studies reporting on a total of 1107 patients were included in the meta-analysis. Six and 3 reported data of acute and late skin toxicity, while 2 studies provided information on cardiac events. Pooled results showed no difference in terms of hazard ratio for loco-regional RT versus no loco-regional RT [hazard ratio (HR) = 0.82, 95% confidence interval (CI) 0.63–1.68]. Loco-regional RT was associated with an OS benefit in the subgroup analysis: IIIB-C (loco-regional RT 79.3% vs no loco-regional RT 71.2%, p = 0.027) and T3-T4 (loco-regional RT 82.6% vs no loco-regional RT 76.6%, p = 0.025). No difference was shown in terms of 5-year DFS (loco-regional RT 91.2% vs no loco-regional RT 83%, p = 0.441) and LRRFS (loco-regional RT 98.1% vs no loco-regional RT 92.3%, p = 0.148). There was no significant difference between the groups in terms of acute and late skin toxicities, lymphedema and cardiac events. Conclusions Because of the limitations due to the small number of studies and heterogeneity in the analysis, the present study does not allow to draw any definitive conclusion, highlighting the need for well-controlled trials to determine the effect of loco-regional RT in patients with cN2 having a pathological complete response in the axillary nodes after preoperative chemotherapy., Highlights • The prognostic impact of pCR after primary systemic therapy on DFS and OS has been shown in meta-analyses of randomized phase III trials. • The association of treatment response with loco-regional recurrence has been studied only in retrospective reports. • RNI should be strongly considered in patients with clinically involved lymph nodes regardless of the response to primary systemic therapy, especially in the presence of further risk factors. • In patients with cN2 at diagnosis and ypN0 at surgery after PST, loco-regional RT should be evaluated for each patient in the multidisciplinary team.

BACKGROUND: Osteosarcoma is a malignant bone tumor affecting mainly children and young adults and commonly involves extremities. The aim of this study was to assess the patient-related, tumor-related, and treatment-related factors affecting the overall survival in patients with non-metastatic extremity osteosarcoma. METHODOLOGY: A retrospective, single institutional study of 100 patients with non-metastatic extremity osteosarcoma was done between 2014 and 2019. Age, sex, histologic type, tumor site, use of preoperative chemotherapy and its duration, response to chemotherapy, type of surgery, presence of local recurrence, occurrence of lung metastasis, and survival data were recorded. Survival analysis was done using Kaplan-Meier method. p < 0.05 by log-rank test was considered statistically significant. Statistical data were analyzed using SPSS v.25(IBM). RESULTS: The median age of presentation was 18 years with male sex preponderance. The most common site of presentation was distal femur, and commonest histological variant was osteoblastic osteosarcoma. Incidence of local recurrence was 9%, and lung metastasis was identified in 12% on follow-up. The 5-year overall survival (OS) was 65.5%, and 5-year local recurrence-free survival was 57.6%. The 5-year OS in neoadjuvant chemotherapy group was 80% compared to 39.5% in upfront surgery group (p = 0.015). The 5-year OS in patients with tumor necrosis > 90% and < 90% was 93.2% and 71.2%, respectively (p = 0.038). The 5-year OS in patients without lung metastasis was 76%, whereas none who developed lung metastasis has survived 5 years (p < 0.001). CONCLUSION: The use of neoadjuvant chemotherapy, good response to chemotherapy, and the absence of lung metastasis on follow-up can independently predict better overall survival.

Background/aim Neoadjuvant or perioperative chemotherapy is the standard treatment for locally advanced gastric cancer. However, in Eastern countries this is still debated. The aim of our study was to evaluate the survival impact of neoadjuvant chemotherapy. Patients and methods A total of 60 patients who underwent preoperative chemotherapy were compared to patients with locally advanced gastric cancer that underwent upfront surgery. Results Median survival of the entire group curatively treated was 41 months with a median progression-free survival of 38 months. By excluding patients with stage IV disease from the neoadjuvant group, a statistically significant difference was reached both in terms of overall survival and disease-free survival. By subdividing patients according to pTNM stages, neoadjuvant patients showed better survival in stage I and II. Conclusion Neoadjuvant chemotherapy could be an effective treatment for locally advanced disease. However, randomized studies are still needed to fully understand its role and identify patients that will benefit from it.

Locally advanced rectal cancer requires multidisciplinary care. In the United States, most patients are treated with neoadjuvant chemoradiation delivered over 25‐28 days, total mesorectal excision, and 4 months of adjuvant chemotherapy. While effective, this trimodal approach is arduous. Alternative approaches have emerged to streamline treatment without sacrificing oncologic outcomes. These approaches include preoperative chemotherapy with selective use of radiation, short‐course radiotherapy delivered over 5 days, and total neoadjuvant therapy with attempted nonoperative organ‐preserving management (watch and wait). Ongoing trials are assessing the efficacies of these approaches in combination with various risk stratification strategies.

Lung cancer is the leading cause of cancer-related death worldwide and in China (1). According to the statistics of the National Cancer Center of China, there were 733,300 new cases of non-small cell lung cancer (NSCLC) and approximately 610,200 related deaths in 2015 (2). For patients with early staged disease, surgery is the mainstay of treatment, and it is commonly followed by adjuvant chemotherapy for patients with locally advanced resectable NSCLC. Although complete surgical resection may be curative for NSCLC, 25–70% of patients (with different proportion according to stage) eventually relapse despite complete resection (3). Platinum-based adjuvant chemotherapy has been shown to marginally increase the 5-year survival rate of patients by 4–8% (4-6). Even after treatment with surgery and indicated adjuvant therapies in eligible cases, approximately 20–30% of stage I, 50% of stage II, and 60% of stage IIIA patients still die within 5 years (7). In the past decade, experts have conducted a number of investigations on the perioperative management of resectable NSCLC; however, progress remains slow, and patients still have a high risk of recurrence and death. Neoadjuvant therapy is defined as any therapy delivered prior to definitive local therapy intended to increase the cure rate. It provides several theoretical benefits in managing such patients with NSCLC. In the setting of, neoadjuvant therapy given prior to radical surgery this approach can also have the goals of downstaging, improving the resection rate, and more promptly treating subclinical micro-metastases than adjuvant approaches, delivered after the definitive local therapy. In addition, the compliance with neoadjuvant therapy has been shown to be better than in the adjuvant setting, and the biological effect of the neoadjuvant therapy can be analyzed directly in the resected tumor specimens (8). A meta-analysis on patients with stage IB‒IIIA NSCLC that compared chemotherapy plus subsequent surgery vs. surgery alone showed that the 5-year survival rate was 5% higher after receiving neoadjuvant chemotherapy (NCT) (9). Therefore, the comprehensive NSCLC data suggest that, for resectable NSCLC, NCT improves survival compared with surgery alone but appear to show no significant survival benefit compared with adjuvant chemotherapy (10). In the last 5 years, immune checkpoint inhibitors (ICIs) have profoundly changed the treatment paradigm for patients with advanced NSCLC (11-15). Immunotherapy has provided hope for long-term survival benefits to a minority of patients with metastatic lung cancer. For treatment-naive patients with driver mutation-negative NSCLC, the 5-year survival rate of single agent pembrolizumab was 23.2%; for the previously treated patients with driver mutation-negative NSCLC, the 5-year survival rates of single agent pembrolizumab and nivolumab were 15.5% and 16%, respectively (16,17). Given the profound impact made by immunotherapy drugs for patients with advanced disease, significant attention has been directed in recent years toward investigating the potential role for early-stage NSCLC patients, and whether they, too, can achieve long-term benefits from the inclusion of immunotherapy into their treatment algorithms. Many phase Ib/II clinical trials have reported promising results, and a series of large-scale phase III clinical trials are underway. However, these various investigations have employed different strategies of neoadjuvant immunotherapy, in terms of the specific regimens as well as number of treatment cycles (18). To better guide Chinese thoracic surgeons in the neoadjuvant immunotherapy of NSCLC, well-known thoracic surgeons in China participated in an in-depth discussion on the hot topics and controversial issues of neoadjuvant immunotherapy and formed the Expert consensus on neoadjuvant immunotherapy for non-small-cell lung cancer by incorporating the latest evidence on neoadjuvant immunotherapy.

Objectives To assess the impact of two cycles of neoadjuvant chemotherapy (NAC) in patients who underwent nephroureterectomy for high-risk cN0M0 upper tract urothelial carcinoma (UTUC), and to evaluate the efficacy of NAC in patients with localised disease (≤cT2). Patients and methods We retrospectively analysed patients with high-risk cN0M0 UTUC who received NAC followed by surgery, compared with a matched cohort who underwent initial surgery at Fujita Health University during 2005-2019. Baseline and tumour characteristics, overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) were compared between the cohorts. Cox proportional hazards models were used to identify predictors of survival. Results There were 117 and 67 patients in the study group and the control group, respectively. Significantly higher pathological downstaging (pDS) and lower lymphovascular invasion (LVI) were observed in the study group than in the control group (48% vs 22%, P = 0.008 and 29% vs 46%, P = 0.045, respectively). The NAC group had significantly better 5-year OS (79% vs 53%, P = 0.003), 5-year CSS (84% vs 66%, P = 0.008), and 5-year RFS (80% vs 61%, P = 0.001) than the control group. The OS benefit of NAC was observed even in patients with localised (≤cT2) disease (P = 0.019). Patients with LVI showed significantly worse CSS both in pathologically locally advanced (≥pT3) and in localised (≤pT2) tumours (P = 0.048 and P = 0.018, respectively). Multivariate analysis identified LVI, NAC, and pDS as independent predictors of OS. Male sex and post-NAC LVI were identified as predictors of worse survival in patients who underwent NAC. Conclusions Two cycles of NAC improved the survival of patients with high-risk UTUC, even in patients with localised disease. Although two cycles of NAC appear to be effective in cN0M0 high-risk UTUC including localised disease, additional larger sample size multicentre prospective studies comparing short-course NAC regimens followed by surgery and surgery alone are required.

Many patients undergoing hepatectomy for colorectal liver metastases (CRLM) experience recurrence. However, no criteria for screening candidates to undergo repeat hepatectomy (RH) for CRLM have been established. Budding, one form by which colorectal carcinoma malignancies are expressed, is a new pathologic index. This study aimed to analyze prognostic factors, including budding, and to provide criteria for screening candidates to undergo RH for recurrent CRLM. Data of 186 consecutive patients who underwent hepatectomy for CRLM between April 2008 and December 2015 were collected. Survival was calculated using the Kaplan–Meier method. Uni- and multivariate analyses were performed to determine factors significantly affecting mortality. Of 186 patients, 131 experienced recurrence after hepatectomy, with 83 of the 131 patients showing recurrence in the liver, and 52 of these 83 patients undergoing primary surgery at the authors’ institution and having information on budding grade. In the univariate analysis, preoperative chemotherapy, budding grade, extrahepatic metastases, and number of liver metastases at the time of recurrence were associated with overall survival (OS) for the 52 patients. In the multivariate analysis, budding grade and number of liver metastases at the time of recurrence were associated with OS. The study examined simple prognostic factors that could help to screen patients better for RH. Repeat hepatectomy improved the prognosis for patients with recurrent CRLM. The independent prognostic factors for OS were number of liver metastases at recurrence as a conventional factor and budding grade as a new pathologic factor. With budding used as an index, patients who could benefit from hepatectomy can be screened more precisely.

Few studies have focused on conversion surgery for biliary malignancy; thus, it is not clear if this treatment modality can extend the survival of patients with unresectable biliary malignancy. We conducted a multicenter retrospective cohort study to evaluate the surgical outcomes of conversion surgery in this setting and analyze long-term survival. We collected clinical data retrospectively on patients who underwent conversion surgery for biliary malignancy. Twenty-four patients met our inclusion criteria. Preoperative chemotherapy regimens or chemoradiation therapy regimens were administered based on the institutional criteria, and surgical procedures were chosen based on tumor location. Morbidity occurred in 16 patients (66.7%), and 1 patient died of liver failure after surgery. The overall 5-year survival rate following initial therapy was 43.2%, and the median survival time was 57.4 months. The corresponding values following surgery were 38.2% and 34.3 months, respectively. The 5-year survival rate of the 24 patients who received both chemotherapy and surgery was significantly better than that of 110 patients treated with chemotherapy only (p

Background We conducted a prospective cohort study in the Netherlands (RAPCHEM: NCT01279304, BOOG 2010-03) in breast cancer (BC) patients treated with primary systemic therapy (PST), followed by surgery and post-operative radiation therapy (RT) according to a predefined consensus-based study-guideline (SG). The aim of the current analysis is to evaluate adherence to the SG. Methods From January 2011 to January 2015, patients with cT1-2N1 BC treated in 17 Dutch RT Centres were included. Patients with four or more suspicious nodes at imaging were excluded. SG recommended whole breast RT for patients treated with breast conserving therapy. SG on loco(-regional) RT were defined for three risk groups based on the ypN status: (1) ypN0 (low-risk): RT breast and no RT after mastectomy; (2) ypN1 (intermediate-risk): RT breast or chest wall; (3) ypN2 (high-risk): RT breast or chest wall, including regional lymph nodes. Results We included 848 patients: 292 in the low-risk group; 374 in the intermediate-risk group; 182 in the high-risk group. Overall, 64% of the patients was treated according to the SG; 11% received less RT than the predefined target volumes and 25% received more extensive RT than according to the SG. The largest variation was seen in the intermediate risk group, where only 54% was treated according to the SG. Conclusion Substantial deviation from the SG for post-operative RT was observed after PST, especially in patients with an intermediate-risk. Future analyses will evaluate outcome of these patients in relation to risk factors and the actual RT given.

Background The incidence and magnitude of indicators of radiographic response of pancreatic cancer to systemic chemotherapy and (chemo)radiation administered prior to anticipated pancreatectomy are unclear. Methods Sequential computed tomography scans of 226 patients with localized pancreatic cancer who received chemotherapy consisting of 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) or gemcitabine and nanoparticle albumin-bound paclitaxel (GA) with or without (chemo)radiation and who subsequently underwent surgery with curative intent from January 2010 to December 2018 at The University of Texas MD Anderson Cancer Center and Verona University Hospital were re-reviewed and compared. Results Overall, 141 patients (62%) received FOLFIRINOX, 70 (31%) received GA, and 15 (7%) received both; 164 patients (73%) received preoperative (chemo)radiation following chemotherapy and prior to surgery; and 151 (67%), 70 (31%), and 5 (2%) patients had Response Evaluation Criteria in Solid Tumors (RECIST) stable disease, partial response, and progressive disease, respectively. The tumors of 29% of patients with borderline resectable or locally advanced cancer were downstaged after preoperative therapy. Radiographic downstaging was more common with chemotherapy than with (chemo)radiation (24% vs. 6%; p = 0.04), and the median tumor volume loss after chemotherapy was significantly greater than that after (chemo)radiation (28% vs. 17%; p Conclusions Less than one-third of patients treated with FOLFIRINOX or GA with or without (chemo)radiation experienced either RECIST partial response or radiographic downstaging prior to surgery. The incidence of tumor downstaging was higher and the magnitude of tumor volume loss was greater following chemotherapy than after (chemo)radiation.

The clinical significance of discordant radiological and pathological response to preoperative chemotherapy of colorectal liver metastases (CLM) is unknown. From 2011 to 2016, all eligible patients undergoing resection for CLM after preoperative chemotherapy were included at two centres. Patients were categorized according to radiologic response using RECIST as Rad-responders (complete/partial response) or Rad-non responders (stable disease) and according to Blazer et al. pathologic response grade as Path-responders (complete/major response) or Path-non responders (minor response). Survival outcome was analysed according to radiologic and pathologic response. Among 413 patients undergoing resection of CLM, 119 fulfilled the inclusion criteria. Among these, 52 (44%) had discordant radiologic and pathologic response including 27 Rad-non responders/path responders and 25 Rad-responders/Path-non responders. Rad-non responders/path responders and Rad-responders/Path-non responders had similar characteristics except for the proportion receiving more than 6 cycles of preoperative chemotherapy (7/27 vs 16/25; P = 0.017). Median disease-free survival was not different in patients with or without discordant radiologic and pathologic responses (P = 0.195) but the type of discordance had an impact on oncologic outcome as median disease-free survival was 13.9 months (95% CI 5.7–22.2 months) in Rad-non responders/Path responders and 8.6 (6.2 – 10.9 months) in Rad-responders/Path-non responders (P = 0.034). Univariate and multivariate analysis showed that major pathologic response was associated with improved disease-free survival (OR 0.583, 95% CI 0.36–0.95, P = 0.031). A discordant radiologic and pathologic response is common after preoperative chemotherapy for CLM. In these patients, pathologic response drives oncologic outcome.

Objective: The aim was to investigate whether pathologic complete response (pCR) in the breast is correlated with absence of axillary lymph node metastases at final pathology (ypN0) in patients treated with neoadjuvant systemic therapy (NST) for different breast cancer subtypes. Background: Pathologic complete response rates have improved on account of more effective systemic treatment regimens. Promising results in feasibility trials with percutaneous image-guided tissue sampling for the identification of breast pCR after NST raise the question whether breast surgery is a redundant procedure. Thereby, the need for axillary surgery should be reconsidered as well. Methods: Patients diagnosed with cT1-3N0-1 breast cancer and treated with NST, followed by surgery between 2010 and 2016, were selected from the Netherlands Cancer Registry. Patients were compared according to the pathologic response of the primary tumor with associated pathologic axillary outcome. Multivariable analysis was performed to determine clinicopathological variables correlated with ypN0. Results: A total of 4084 patients were included for analyses, of whom 986 (24.1%) achieved breast pCR. In clinically node negative patients (cN0), 97.7% (432/442) with breast pCR had ypN0 compared with 71.6% (882/1232) without breast pCR (P

Imaging has a key role in the assessment of paediatric renal tumours, especially when the initial treatment approach is to proceed to standard chemotherapy without histological confirmation. In Europe, according to the International Society of Paediatric Oncology guidelines, core needle biopsy is not routinely done unless the child is older than 10 years. Between age 6 months and 9 years, the child is treated with a standard regimen of preoperative chemotherapy unless there are concerns about non-Wilms' tumour pathology. Atypical imaging findings could therefore stratify a child into a different treatment protocol, and can prompt the need for pretreatment histology. This review details the latest protocols and techniques used in the assessment of paediatric renal tumours. Important imaging findings are discussed, especially the features that might prompt the need for a pretreatment biopsy. Local radiology practices vary, but both MRI and CT are widely used as routine imaging tests for the assessment of paediatric renal tumours in Europe. Advances in imaging technology and MRI sequences are facilitating the development of new techniques, which might increase the utility of imaging in terms of predicting tumour histology and clinical behaviour. Several of these new imaging techniques are outlined here.

Background The role of preoperative chemotherapy in the treatment of patients with oesophageal squamous cell carcinoma (ESCC) remains controversial. Chemotherapy followed by surgery was compared with surgery ± chemotherapy, and the detection of circulating tumour cells (CTCs) was performed on all enrolled patients. Methods We randomly assigned patients with resectable tumours to the preoperative chemotherapy group (Pre group) or surgery group (patients who were either given or not given adjuvant chemotherapy according to their postoperative lymph node status, Post group). Blood samples were collected 1–3 days before treatment (including preoperative chemotherapy and surgery) and 7 days after surgery for CTC detection. Results From July 2016 to October 2018, 115 patients were enrolled in the study, of whom 57 were assigned to the Pre group and 58 to the Post group. The proportion of patients with stage III ESCC was 63.16% in the Pre group and 48.28% in the Post group. No patients died during chemotherapy. One patient exhibited a complete response to preoperative chemotherapy, and 13 patients exhibited partial responses. The 2-year progression-free survival (PFS) and overall survival (OS) rates were not significantly different between the Pre and Post groups. In the subgroup analysis, patients with CTC (+) prior to treatments receiving preoperative chemotherapy had a better 2-year PFS (71.90% vs. 38.73%, P = 0.0379). In the Cox proportional hazards regression analysis, platelet count was proven to correlate significantly with disease progression (P = 0.016), and no factors were proven to correlate significantly with mortality after the factors were balanced in the present analysis. Conclusions Preoperative chemotherapy improved the short-term PFS when CTC detection was positive prior to any treatment for patients with stage II or III ESCC. CTC detection may be used as an index to guide individualized strategic decisions regarding preoperative chemotherapy, but more evidence is needed.

Introduction Total pathologic complete response (tpCR; ypT0/is ypN0) after preoperative chemotherapy (PCT) is associated with better outcome in locally advanced breast cancers. However, the tpCR rate according to histology is not usually considered in trials. Material and methods Patients with invasive lobular breast carcinoma (ILC), who were included in three phase II trials (AT, ATX, and TXH), were eligible. Expression of markers and clinical phenotypes (CPh) were determined by immunohistochemistry. The primary endpoint was tpCR rate in patients with ILC. Secondary endpoints were breast-conserving surgery rate (BCSR), event-free survival (EFS), and overall survival (OS). Results In the subgroup of patients with ILC (n = 16) the median age was 50 years, 56.25% were premenopausal, median tumour size was 5 cm, and 68.75% had clinically node involvement. Six patients (37.5%) had clinical stage II, and 10 (62.5%) had clinical stage III. Hormone receptor-positive disease was present in 93.75% of the patients, and median Ki-67 was 25%. CPh were Luminal A-like in 37.5%, Luminal B-like in 50%, HER2-positive in 6.25%, and triple negative in 6.25% of tumours. Only one patient (6.25%) had a tpCR, and another patient had a pathologic complete response (pCR) only in the breast. With a median follow-up of 146 months, median EFS was 120 months (95% CI: 68-139), and median OS was not reached. Ten-year EFS and OS probability were 47% and 60%, respectively. BCSR was only 12.5%. Conclusions PCT in patients with ILC is associated with low tpCR rate because the majority of these patients have Luminal tumours with low chemo-sensitivity.

Introduction of sentinel lymph node biopsy, initially in clinically node-negative and subsequently in patients presenting with involved axilla and downstaged by primary systemic therapy, allowed for significant decrease in morbidity compared to axillary lymph node dissection. Concurrently, regional nodal irradiation was demonstrated to improve outcomes in most node-positive patients. Additionally, over the last decades, introduction of more effective systemic therapies has resulted in improvements not only at distant sites, but also in locoregional control, creating space for de-escalation of locoregional treatments. We discuss the data on de-escalation in axillary surgery and irradiation, both in patients undergoing upfront surgery and primary systemic therapy, with special emphasis on the feasibility of omission of nodal irradiation in patients undergoing primary systemic therapy. In view of the accumulating evidence, omission of axillary irradiation may be considered in clinically node-positive patients converting after primary systemic therapy to pathologically negative nodes on sentinel lymph node biopsy (preferably also with in-breast pCR), presenting with lower initial nodal stage, older age and were treated with breast-conserving surgery followed by whole breast irradiation. Omission of regional nodal irradiation in patients with aggressive tumor phenotypes achieving a pCR is under investigation. In patients undergoing preoperative endocrine therapy the adoption of axillary management strategies utilized in case of upfront surgery seems more suitable than those used in post chemotherapy-based primary systemic therapy setting.

Systemic relapses remain a major problem in locally advanced rectal cancer. Using short-course radiotherapy followed by chemotherapy and delayed surgery, the Rectal cancer And Preoperative Induction therapy followed by Dedicated Operation (RAPIDO) trial aimed to reduce distant metastases without compromising locoregional control.In this multicentre, open-label, randomised, controlled, phase 3 trial, participants were recruited from 54 centres in the Netherlands, Sweden, Spain, Slovenia, Denmark, Norway, and the USA. Patients were eligible if they were aged 18 years or older, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, had a biopsy-proven, newly diagnosed, primary, locally advanced rectal adenocarcinoma, which was classified as high risk on pelvic MRI (with at least one of the following criteria: clinical tumour [cT] stage cT4a or cT4b, extramural vascular invasion, clinical nodal [cN] stage cN2, involved mesorectal fascia, or enlarged lateral lymph nodes), were mentally and physically fit for chemotherapy, and could be assessed for staging within 5 weeks before randomisation. Eligible participants were randomly assigned (1:1), using a management system with a randomly varying block design (each block size randomly chosen to contain two to four allocations), stratified by centre, ECOG performance status, cT stage, and cN stage, to either the experimental or standard of care group. All investigators remained masked for the primary endpoint until a prespecified number of events was reached. Patients allocated to the experimental treatment group received short-course radiotherapy (5 × 5 Gy over a maximum of 8 days) followed by six cycles of CAPOX chemotherapy (capecitabine 1000 mg/mBetween June 21, 2011, and June 2, 2016, 920 patients were enrolled and randomly assigned to a treatment, of whom 912 were eligible (462 in the experimental group; 450 in the standard of care group). Median follow-up was 4·6 years (IQR 3·5-5·5). At 3 years after randomisation, the cumulative probability of disease-related treatment failure was 23·7% (95% CI 19·8-27·6) in the experimental group versus 30·4% (26·1-34·6) in the standard of care group (hazard ratio 0·75, 95% CI 0·60-0·95; p=0·019). The most common grade 3 or higher adverse event during preoperative therapy in both groups was diarrhoea (81 [18%] of 460 patients in the experimental group and 41 [9%] of 441 in the standard of care group) and neurological toxicity during adjuvant chemotherapy in the standard of care group (16 [9%] of 187 patients). Serious adverse events occurred in 177 (38%) of 460 participants in the experimental group and, in the standard of care group, in 87 (34%) of 254 patients without adjuvant chemotherapy and in 64 (34%) of 187 with adjuvant chemotherapy. Treatment-related deaths occurred in four participants in the experimental group (one cardiac arrest, one pulmonary embolism, two infectious complications) and in four participants in the standard of care group (one pulmonary embolism, one neutropenic sepsis, one aspiration, one suicide due to severe depression).The observed decreased probability of disease-related treatment failure in the experimental group is probably indicative of the increased efficacy of preoperative chemotherapy as opposed to adjuvant chemotherapy in this setting. Therefore, the experimental treatment can be considered as a new standard of care in high-risk locally advanced rectal cancer.Dutch Cancer Foundation, Swedish Cancer Society, Spanish Ministry of Economy and Competitiveness, and Spanish Clinical Research Network.

ObjectiveTo correlate peripheral enhancement on contrast-enhanced computed tomography (CE-CT) of post-chemotherapy colorectal liver metastases (CRLM) patients with the pathological findings.MethodsForty-four patients with CRLM who underwent hepatic resection after preoperative chemotherapy between 2008 and 2013 were included. Two radiologists blinded to the histopathology findings performed a consensus categorization of the marginal contrast effects of CRLM on CE-CT as follows: Group 1, smooth margin without enhancement; Group 2, smooth margin with an enhanced rim; and Group 3, fuzzy margin with/without an enhanced rim. The Kruskal-Wallis test was used to compare the imaging findings with the histological findings.ResultsThe percentage of infarct-like necrosis was significantly higher in CRLM with smooth margins than in those with fuzzy margins (pConclusionsOur findings suggest that the type of necrosis is related to the nature of the margins, and the presence of residual cells are related to peripheral enhancement.Advances in knowledgeIn CRLM, following chemotherapy, the presence of residual cells and dangerous haloes is related to the contrast effect of the tumor margins, suggesting that tumor angiogenesis affects the contrast effect.

Although the road that led to a generalized consensus was arduous, D2 lymphadenectomy is currently the standard of care for locally advanced gastric cancer, according to most of the recent European guidelines. The indication to extend lymphadenectomy beyond D2 is still debated. In agreement with Japanese authors, para-aortic nodes should be removed in a “curative” setting in patients who have clinical evidence of para-aortic nodes before preoperative chemotherapy and then show clinical response at restaging examinations. But there are likely some patients that would benefit also from “prophylactic” para-aortic dissection in the context of a multimodal treatment; the role of removing the other posterior stations should be further evaluated too. Another important issue is the evaluation of compliance to standard lymphadenectomy. A recent study showed that European dedicated surgeons perform an adequate dissection (>15 nodes) in nearly all treated patients. However, there is still a high variability in the approach to D2, with the major determinants being tumor histology and the patient’s general condition. This raises the question of whether a certain level of variability would reflect more likely the efforts by expert surgeons to choose the best treatment for their individual patients rather than technical issues.

Background: In this retrospective cohort study, the potential of gemcitabine (gem)/cisplatin (cis) chemotherapy as future preoperative therapy for patients with unresectable locally advanced or borderline resectable intrahepatic, perihilar, and mid-cholangiocarcinoma was investigated. Methods: All patients with intrahepatic, perihilar, and mid-cholangiocarcinoma presented at Amsterdam UMC between January 2016 and October 2019 were included. The radiologic response after 3 and/or 6 cycles of gem/cis chemotherapy in patients with unresectable locally advanced or borderline resectable disease was derived from the original radiologic reports and subsequently re-evaluated for surgical exploration by consensus reading of 2 HPB surgeons and 1 radiologist. Results: Overall, 65 of 364 patients had a locally advanced or borderline resectable disease. Twenty-eight patients were treated with palliative chemotherapy, including 25 (89.3%) patients who received more than 3 cycles. Twenty-two patients (88.0%) and 13 patients (46.4%) showed RECIST stable disease or partial response after 3 and 6 cycles of chemotherapy, respectively. Three patients experienced grade 3 adverse events. Consensus reading concluded that exploration could have been reconsidered in 7 of 28 patients (25.0%). Conclusion: Gem/cis may be a safe and feasible preoperative treatment in initially unresectable locally advanced or borderline resectable cholangiocarcinoma. In addition, the findings of this study support to always rediscuss patients with stable or responsive disease in multidisciplinary team meetings to reconsider resection. Besides, prospective studies are needed to investigate this effect further and, based on these preliminary data, seem feasible in this setting.

BackgroundFor gastric cancer (GC) with extensive lymph node metastasis (bulky N2 and/or para-aortic lymph node metastases), there is no standard therapy worldwide. In Japan, preoperative chemotherapy (PCT) followed by D2 gastrectomy plus para-aortic lymph node dissection (PAND) is considered the standard treatment for these patients. However, in China, the standard operation for GC patients with only bulky N2 metastases was D2 gastrectomy. Besides, after PCT, whether doing PAND improves survival or not is debatable for GC patients with para-aortic lymph node (PAN) metastases. Therefore, we conducted this study to investigate whether D2 lymphadenectomy alone is suitable for these patients after PCT.MethodsWe retrospectively collected data on patients from our electronic medical record system. GC patients with bulky N2 and/or PAN metastases who underwent D2 lymphadenectomy alone after PCT were enrolled. The survival outcomes and chemotherapy responses were analyzed and compared with the results of the JCOG0405 study.ResultsFrom May 2009 to December 2017, a total of 83 patients met all eligibility criteria and were enrolled. The median survival duration for all patients was 40.0 months. The 3-year and 5-year OS rates for all patients were 50.3% and 45.6%, respectively. For patients with only bulky N2 metastasis, the 3-year and 5-year OS rates were 77.1% and 71.6%, respectively, which were similar to the results of the JCOG0405 study (82.7% and 73.4%). For patients with only PAN metastases, the 3-year and 5-year OS rates were 50.0% and 50.0%, respectively, which seemed to be lower than those of the JCOG0405 study (64.3% and 57.1%). For patients with bulky N2 and PAN metastases, the 3-year and 5-year OS rates were 7.4% and 0.0%, respectively, which were lower than those of the JCOG0405 study (20.0% and 20.0%).ConclusionThe results of our study suggest that D2 lymphadenectomy alone is suitable for GC patients with only bulky N2 metastasis after PCT. However, D2 lymphadenectomy alone perhaps is not suitable for patients with bulky N2 and PAN metastases after PCT.

The treatment of lung cancer is one of the major challenges in the field of oncology. According to statistics from the National Cancer Center of China in 2015, lung cancer has the highest incidence and mortality, with 733,300 new cases and 610,200 deaths across the country (1). About 85% of lung cancers are non-small cell lung cancer (NSCLC), of which 30% to 40% are considered resectable tumors, including most stage I-II and a small portion of stage IIIA tumors (2). Very early-stage NSCLC (IA) can be cured by surgery. However, more than 50% of NSCLC patients who undergo surgical treatment will relapse or metastasize within 5 years. Even if there is no lymph node metastasis and the primary

Perforation of esophageal cancer solely due to preoperative chemotherapy is extremely rare, but can be associated with pyothorax and can be difficult to treat. Here, we report the case of a successfully treated patient with thoracic esophageal cancer who had esophageal perforation during docetaxel, cisplatin, and 5-fluorouracil chemotherapy. A 73-year-old patient had esophageal perforation on the fourth day of the first docetaxel, cisplatin, 5-fluorouracil cycle. The second docetaxel, cisplatin, 5-fluorouracil cycle was administered after insertion of esophageal stenting and subtotal esophagectomy. Early drainage and stent placement were crucial for achieving infection control and allowing for a subsequent complete resection.

Introduction: This retrospective study conducted at the Department of Pathology, Government Medical College, Thiruvananthapuram, Kerala, India, included all cases of Neuroblastomas received during the 5year period- January 2004 to December 2008. Materials and Methods: Resected specimens and Incisional biopsy specimen’s/ lymph nodes of size more than 2x2 cm were included as per International Neuroblastoma Pathology Committee (I.N.P.C) criteria. The specimens were then classified into Undifferentiated (confirmed by Immunohistochemistry), Poorly Differentiated and Differentiating. Patient details and 3 year Follow up were obtained by communication with treating doctors and reviewing hospital records. Results: During the 5 year period we received 38 specimens of Neuroblastomas, one specimen was rejected as it was less than 2x2 cms. The study was hence carried forth on 37 cases- 27 post-chemotherap y and 10 pre-chemotherapy. The Clinicopathologic features studied included Age, Sex, Clinical presentation, Tumor location, Preoperative Chemotherapy and the Gross and Microscopic features. Mitotic Karyorrhectic Index (M.K.I) was determined in the ten pre-chemotherapy cases. Conclusion: The Ten Pre-chemotherapy Neuroblastomas were subclassified into Favorable and Unfavorable histology based on three parameters- Age, Histological Differentiation and M.K.I. Five cases belonged to Favorable group and Five to the Unfavorable group. One case was lost to follow up from both the groups respectively. The remaining 4 Favorable cases are doing well on follow up. In the Unfavorable group 3 cases expired and 1 is doing well. As M.K.I could not be determined, the 27 post -chemotherapy cases were followed up with age and histologic differentiation alone. Keywords: Neuroblastoma, Immunohistochemistry, Mitotic Karyorrhectic Index (M.K.I).

Summary: Background/objective: The role of gastrectomy for stage IV gastric cancer (GC) has not yet been established. Thus, we aimed to compare the prognoses of patients with clinical stage IV GC who underwent gastrectomy with and without preoperative chemotherapy after precise recategorization of patients. Methods: We retrospectively reviewed a total of 92 clinical stage IV GC patients who underwent gastrectomy with or without preoperative chemotherapy between 2010 and 2016 at a single institution. Yoshida's classification was used to categorize the patients into the following categories: 1, technically resectable metastasis; 2, marginally resectable metastasis; 3, unresectable peritoneal dissemination; and 4, incurable peritoneal dissemination with distant organ metastasis. Two-year disease-specific survival (DSS) rates were compared between patients who underwent primary surgery and preoperative chemotherapy for each category. Results: The two-year DSS rates of primary surgery vs. preoperative chemotherapy in Categories 1, 2, 3, and 4 (n = 35, 39, 14, and 4, respectively) were 48.6% vs. 41.7% (p = 0.829), 52.6% vs. 40.0% (p = 0.855), 50.0% vs. 75.0% (p = 0.027), and 0% vs. 66.7% (p = 0.083), respectively. Patients in Categories 1 and 2 who underwent preoperative chemotherapy tended to have lower two-year DSS rates (p = 0.911), whereas patients in Categories 3 and 4 had significantly higher two-year DSS rates than those who underwent primary surgery (p = 0.014). Conclusions: Primary surgery may be performed in patients without peritoneal dissemination when GC is technically resectable. However, if peritoneal dissemination is suspected, chemotherapy should be prioritized. Keywords: Carcinomatosis, Chemotherapy, Gastrectomy, Gastric adenocarcinoma

Purpose of the study. To study the possibilities of 99mTc-MIBI single photon emission computed tomography (SPECT) at the monitoring of the preoperative treatment of patients with laryngeal and hypopharyngeal cancer. Materials and methods. The study included 28 pa tients with cancer of the larynx or laryngopharynx T2–3N0–2M0. 99mTc-MIBI SPECT was performed for all patients before and after preoperative treatment, semi-quantitative indices were calculated, according to SPECT Results. A statistically significant difference was observed in the retention index in patients with complete regression and stabilization. A lower retention index is observed in patients who had a clinically pronounced effect from preoperative treatment. The rate of radiotracer washout from the tumor was faster in patients with no effect of preoperative therapy. The level of radiopharmaceuticals uptake in the tumor tissue after preoperative treatment was significantly lower in the group of patients without progression than in the group of patients with progression of the disease. In addition, the accumulation of the radioindicator after preoperative chemotherapy increased in the group of patients with progression, and decreased in the group without progression.Conclusion. The 99mTc-MIBI SPECT for tumor monitoring during treatment can be used. Semi-quantitative indices can be used as predictive criteria of results of preoperative treatment, as well as prognostic criteria for monitoring of such patients.

Although surgical resection is the only treatment of choice that can offer prolonged survival and a chance of cure in patients with colorectal liver metastases (CRLM), nearly 80% of patients are deemed to be unresectable at the time of diagnosis. Considerable efforts have been made to overcome this initial unresectability, including expanding the indication of surgery, the advent of conversion chemotherapy, and development and modification of specific surgical techniques, regulated under multidisciplinary approaches. In terms of specific surgical techniques, portal vein ligation/embolization can increase the volume of future liver remnant and thereby reduce the risk of hepatic insufficiency and death after major hepatectomy. For multiple bilobar CRLM that were traditionally considered unresectable even with preoperative chemotherapy and portal vein embolization, two‐stage hepatectomy was introduced and has been adopted worldwide with acceptable short‐ and long‐term outcomes. Recently, ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) was reported as a novel variant of two‐stage hepatectomy. Although issues regarding safety remain unresolved, rapid future liver remnant hypertrophy and subsequent shorter intervals between the two stages lead to a higher feasibility rate, reaching 98%. In addition, adding radiofrequency ablation and vascular resection and reconstruction techniques can allow expansion of the pool of patients with CRLM who are candidates for liver resection and thus a cure. In this review, we discuss specific techniques that may expand the criteria for resectability in patients with initially unresectable CRLM.

Postoperative complications affect both the short-term and long-term outcomes. The aim of this study was to identify specific prognostic factors among complications after hepatectomy for colorectal liver metastasis (CRLM).Between 2002 and 2014, 427 patients underwent initial hepatectomy for CRLM. The clinicopathological parameters including postoperative complications were evaluated to identify the prognostic factors for the overall (OS) and relapse-free survival (RFS).One hundred and forty-nine patients (34%) developed postoperative complications, including surgical site infection (n = 49, 11.4%), bile leakage (n = 41, 9.6%), posthepatectomy liver failure (PHLF) (n = 26, 6.0%), and pulmonary complication (n = 20, 4.6%). The independent predictors of RFS included primary nodal metastasis, abnormal CA19-9 levels, extrahepatic metastasis, bilateral CRLMs, ≥5 CRLMs, preoperative chemotherapy, lack of adjuvant chemotherapy and PHLF. The 5-year RFS rates in patients with and without PHLF were 8% and 32%, respectively (P 0.001). The independent prognostic factors for OS included primary nodal metastasis, abnormal CA19-9 levels, extrahepatic metastasis, positive surgical margins, preoperative chemotherapy, lack of adjuvant chemotherapy and PHLF. The 5-year OS rates in patients with and without PHLF were 31% and 63%, respectively (P = 0.004).Among the complications, only PHLF was associated with decreased long-term survival after hepatectomy for CRLM as well as tumor-specific prognostic factors.

OBJECTIVE: We sought to identify potential radiologic and serologic markers of pancreatic tumor response to therapy, using pathologic major response (pMR) as the objective endpoint. BACKGROUND: We previously demonstrated that a pMR to preoperative therapy, defined as detection of

Background Delaying radical cystectomy (RC) after a diagnosis of muscle-invasive bladder cancer (MIBC) has been associated with adverse survival. However, data are lacking regarding the impact of RC delay in patients receiving neoadjuvant chemotherapy (NAC). Objectives To assess whether the time from last cycle of NAC to RC (time to cystectomy, TTC) is associated with survival among MIBC patients. Design, setting, and participants The study cohort comprised 226 patients treated with NAC and RC between 1999 and 2015 for cT2–T4N0M0 bladder cancer. Outcome measurements and statistical analysis Descriptive statistics were used to test the association between TTC and clinicopathologic variables. Overall mortality (OM) and cancer-specific mortality (CSM) were analyzed via Kaplan-Meier estimation according to TTC. We assessed factors associated with OM and CSM using multivariable Cox regression analyses. Results and limitations The median TTC was 7.57 wk (interquartile range 5.2–10.8). Patients with a Charlson comorbidity index (CCI) ≥1 had a longer TTC than those with a score of 10 wk had significantly lower OM-free (p = 0.003) and CSM-free rates (p Conclusions TTC of >10 wk after NAC was associated with adverse survival among patients with MIBC. Patients with a higher CCI were more likely to have prolonged TTC. Patient summary The impact of delaying radical cystectomy in patients who have received neoadjuvant chemotherapy (NAC) is unknown. In this study we assessed whether prolonged time to cystectomy (TTC) after NAC affects survival outcomes in patients with muscle-invasive bladder cancer. We found that TTC of >10 wk was associated with adverse overall survival and cancer-specific survival, and attempts should be made to shorten TTC after preoperative chemotherapy.

Background Hepatic surgery is appropriate for selected patients with colorectal liver metastases (CRLM). Advances in chemotherapy have led to modification of management, particularly when metastases disappear. Treatment should address all initial CRLM sites based on pretherapeutic cross-sectional imaging. This study aimed to evaluate pretherapeutic fiducial marker placement to optimize CRLM treatment. Methods This pilot investigation included patients with CRLM who were considered for potentially curative treatment between 2009 and 2016. According to a multidisciplinary team decision, lesions smaller than 25 mm in diameter that were more than 10 mm deep in the hepatic parenchyma and located outside the field of a planned resection were marked. Complication rates and clinicopathological data were analysed. Results Some 76 metastases were marked in 43 patients among 217 patients with CRLM treated with curative intent. Of these, 23 marked CRLM (30 per cent), with a mean(s.d.) size of 11·0(3·4) mm, disappeared with preoperative chemotherapy. There were four complications associated with marking: two intrahepatic haematomas, one fiducial migration and one misplacement. After a median follow-up of 47·7 (range 18·1-144·9) months, no needle-track seeding was noted. Of four disappearing CRLM that were marked and resected, two presented with persistent active disease. Other missing lesions were treated with thermoablation. Conclusion Pretherapeutic fiducial marker placement appears useful for the curative management of CRLM.

International audience; BACKGROUND:Two-stage hepatectomy of bilobar colorectal liver metastases is widely used and shows encouraging survival results. However, the risk of dropout after the first stage remains high and is associated with poor survival. The objective of our study was to evaluate the factors associated with long-term survival based on the pathologic response to preoperative systemic chemotherapy in colorectal liver metastases patients who underwent two-stage hepatectomy.METHODS:The pathologic response to preoperative chemotherapy and its effect on second-stage completion and survival were retrospectively evaluated in 67 patients treated between 2003 and 2013.RESULTS:A total of 56 patients underwent two-stage hepatectomy for initially nonresectable colorectal liver metastases. Chemotherapy was combined with a biotherapy in 32 cases. The tumor regression grade, modified tumor regression grade, and Blazer grade were used to classify patients as responders (tumor regression grade and modified tumor regression grade 1-3, Blazer 0-1) or nonresponders (tumor regression grade and modified tumor regression grade 4-5, Blazer 2) after the first stage. Tumor response in the three classifications was associated with second-stage completion (tumor regression grade 1-3: OR = 4.01, 95% CI: 1.12-14.36, P = .033; modified tumor regression grade 1-3: OR = 3.8, 95% CI: 1.13-12.6, P = .03; Blazer 0-1: OR = 5.45, 95% CI: 1.66-17.85, P = .005). Triple chemotherapy was also associated with responders. The median overall survival of responders was significantly higher (Blazer 0-1: 42.9 months versus Blazer 2: 20.1 months, P = .018; tumor regression grade 1-3: 42.9 months versus tumor regression grade 4-5: 25.1 months, P = .04).CONCLUSION:A pathologic response to chemotherapy is associated with second-stage completion and longer survival. Further studies are needed to achieve the early identification of patients for whom the benefit of the second surgical stage is less straightforward.

Background: Bile leaks are one of the most common complications after liver resection. The International Study Group of Liver Surgery (ISGLS) established a uniform bile leak definition including a severity grading. However, a risk factor assessment according to ISGLS grading as well as the clinical implications has not been studied sufficiently so far. Methods: The incidence and grading of bile leaks according to ISGLS were prospectively documented in 501 consecutive liver resections between July 2012 and December 2016. A multivariate regression analysis was performed for risk factor assessment. Association with other surgical complications, 90-day mortality as well as length of hospital stay (LOS) was studied. Results: The total rate of bile leaks in this cohort was 14.0%: 2.8% grade A, 8.0% grade B, and 3.2% grade C bile leaks were observed. Preoperative chemotherapy or biliary intervention, diagnosis of hilar cholangiocarcinoma, colorectal metastasis, central minor liver resection, major hepatectomy, extended hepatectomy or two-stage hepatectomy, were some of the risk factors leading to bile leaks. The multivariate regression analysis revealed that preoperative chemotherapy, major hepatectomy and biliodigestive reconstruction remained significant independent risk factors for bile leaks. Grade C bile leaks were associated not only with surgical site infection, but also with an increased 90-day mortality and prolonged LOS. Conclusions: The preoperative treatment as well as the surgical procedure had significant influence on the incidence and the severity of bile leaks. Grade C bile leaks were clinically most relevant, and led to significant increased LOS, rate of infection, and mortality.

BACKGROUND The self-expandable metal stent is used as a bridge to surgery in the treatment of acute malignant colorectal obstruction (AMCO). However, recent studies have shown inferior long-term outcomes and increased risk of tumor dissemination after stent placement. In addition, the optimal interval between stent placement and surgery is not clear. The aim of the current study was to present a new strategy for AMCO: stent placement followed by preoperative chemotherapy and elective surgery. CASE SUMMARY Six patients were diagnosed as acute obstruction. There was one patient with descending cancer, four with sigmoid cancers and one with rectal cancer. The obstructive symptoms of these six patients were relieved within 3 d after stent placement. After receiving two cycles of preoperative chemotherapy, consisting of modified infusional fluorouracil, leucovorin and oxaliplatin [modified FOLFOX6 (mFOLFOX6)], they underwent elective surgery of primary tumor resection. None of the 6 patients received colostomy or colonic lavage during surgery. There was no complication of anastomotic leak, ileus or surgical site infection after surgery. In addition, the patients had low operation time and blood loss, adequate lymph nodes harvest and fast postoperative recovery. CONCLUSION The two-cycle mFOLFOX6 preoperative chemotherapy and elective surgery after stent placement is a safe and feasible strategy in the management of AMCO.

Colorectal liver metastases (CLM) are not always resectable at the time of diagnosis. An insufficient future liver remnant is a factor excluding patients from curative intent resection. To deal with this issue, two-stage hepatectomy was introduced approximately 20 years ago. It is a sequential treatment strategy for bilateral CLM, which consists of preoperative chemotherapy, portal vein embolization, and planned first and second liver resections. This study reviews current evidence supporting use of two-stage hepatectomy.

Background The survival impact of specific body composition changes during preoperative chemotherapy in patients with colorectal liver metastases undergoing curative-intent surgery remains unclear. This study aimed to determine the impact of changes in body weight and muscle mass during preoperative chemotherapy on survival after hepatectomy in patients with colorectal liver metastases. Methods Consecutive patients with colorectal liver metastases undergoing preoperative chemotherapy and curative hepatectomy during 2009–2013 were retrospectively analyzed. Recurrence-free and overall survival were examined according to body compositions, including muscle mass, as measured by skeletal muscle index (area of muscle [cm2]/square of height [m2]), and body weight before and after preoperative chemotherapy. Results The median follow-up duration in overall 169 patients was 47 months. Skeletal muscle index and body weight changed significantly during chemotherapy (skeletal muscle index: –0.52 cm2/m2, P = .03; body weight: +1.1 kg, P = .002). Patients with major muscle mass loss (≥7%) had significantly shorter median RFS than patients with no or minor muscle mass loss ( Conclusion Major loss of muscle mass but not body weight loss during preoperative chemotherapy is significantly associated with poor recurrence-free survival after hepatectomy in patients with colorectal liver metastases. The mechanisms mediating this association may inform future trials on maintaining muscle mass with dedicated nutrition and exercise programs to improve outcomes.

The aim of this study was to evaluate the effect of the chemoradiation therapy on the incidence of postoperative complications and mortality rate in patients with locally advanced tumors of the thoracic esophagus.The study included men and women over 18 with histologically verified squamous cell carcinoma of the thoracic esophagus with TNM stage cT3-4aN0-3M0. Patients were divided into two groups: patients in a main group (n=26) received a complex treatment, patients in a second group (n=30) undergoing only surgical treatment.The first stage of treatment was performed for all 26 patients and included 2 courses of preoperative chemotherapy, followed by a chemoradiation therapy with a 44–46 Gy with weekly injections of chemotherapy. Surgical procedure (R0) was performed for 24 patients (92.3 %) in the main group and for 26 (86.6 %) in a second group.Therapeutic complications were developed in 17 (65 %) patients in a first group, while in a second group this rate was in 18 (60 %) patients from 30. The incidence of surgical complications was slightly higher in a group of patients received a complex treatment –7 (26.92 %) patients. In the surgical group such complications was noted in 6 (20 %) patients. The only death in an early postoperative period was in 1 (3.84 %) patient from the main group. The cause was sepsis and the development of multiple organic failure. There were no lethal outcomes in a surgical group.Estimating the incidence of complications, it should be noted that the use of chemoradiation therapy in the neoadjuvant regimen does not significantly affect the course of the postoperative period. The mortality rate was slightly higher in in the group of patients received complex treatment. At the same time, improvement of the ostoperative period and a reduction of mortality rate in group ofpatients undergoing complex treatment is possible due to optimization of preoperative preparation, postoperative management and competent selection of patients.

Microsatellite instability (MSI) and programmed death-ligand 1 (PD-L1) are candidate predictors for the response to immune checkpoint inhibitors, and may predict chemotherapy sensitivity. We investigated the simultaneous expression of mutL homolog 1 (MLH1), a mismatch repair gene, and PD-L1 in gastric cancers. We examined MLH1 and PD-L1 expression in surgical specimens from 285 gastric cancer patients treated with or without preoperative chemotherapy, and assessed the relation between expression results and both histological response and recurrence-free survival (RFS). Of 285 patients, 28 (9.8%) and 70 (24.6%) exhibited negative MLH1 and high PD-L1 expression, respectively. Most MLH1-negative tumors (85.7%) showed high MSI, and these tumors exhibited high PD-L1 expression more frequently than MLH1-positive tumors (57.1% vs. 21.0%, P

Highlights • Preoperative chemotherapy alone for locally advanced rectal cancer remain unclear. • Neoadjuvant chemotherapy was a promising treatment for unresectable rectal cancer. • Earlier preoperative systemic chemotherapy was assumed to prevent the dissemination., Background In Japan, the significance and efficacy of preoperative chemotherapy alone for locally advanced rectal cancer remain controversial. This case report presents the apparent effectiveness of preoperative FOLFOX plus bevacizumab as shown by pathological complete response (pCR). Additionally, we review the relevant literature and discuss the clinical management of locally advanced rectal cancer with preoperative chemotherapy. Case presentation A 59-year-old male presented with severe constipation, bloody stool and a loss of 10% of his body weight over 3 months. Preoperative examination revealed locally advanced rectal cancer with extensive invasion of the bladder wall and enlarged regional lymph nodes. Thus, this lesion was assigned a preoperative classification of T4bN2bM0 stage IIIC according to the 8th Union for International Cancer Control (UICC) guidelines. Therefore, the patient initially underwent an external loop colostomy of the transverse colon. Next, the patient received chemotherapy including FOLFOX plus bevacizumab. After 12 cycles of chemotherapy, the tumor size was markedly decreased, and all lymph node metastases had disappeared. Therefore, the patient underwent conventional resection of the rectum with D3 lymph node dissection and closure of the colostomy. Histopathological analysis of the resected specimen revealed that all lesions were fibrotic and devoid of any viable cancer cells. Thus, this lesion was assigned a final classification of ypT0N0M0 stage 0. Conclusions We present the rare case of a patient with surgically resected locally advanced rectal cancer who demonstrated an impressive pCR with preoperative chemotherapy, which included FOLFOX plus bevacizumab.

Although the incidence of the most frequent malignant gastric tumour, adenocarcinoma, has been decreasing, during the last decades the incidence of proximal localizations of gastric cancer as well as esophagogastric cancer has been increasing. Due to the late detection of initially advanced disease the outcomes of treatment for the patients are unsatisfactory. Diagnosis is set by tumour biopsy during endoscopy. The basis of treatment of locoregional disease is surgery in combination with perioperative chemotherapy. Alternatively, if no preoperative chemotherapy is administered, adjuvant chemoradiotherapy or chemotherapy should be performed. Metastatic disease is treated with palliative chemotherapy and best supportive care. Treatment decisions should be individualized according to patients’ characteristics and made after multidisciplinary team discussion. The following text presents the clinical guidelines in order to standardize the diagnostic procedures, treatment and monitoring of patients with gastric cancers in the Republic of Croatia.

Purpose Perioperative chemotherapy (POC) in advanced gastric cancer (GC) patients significantly increases the curative resection rate and overall survival (OS). Textbook outcome (TO) represents a composite of surgical quality metrics strongly associated with improved OS. However, the current definition of TO after resection for GC does not include POC. Herein we propose to supplement the current description of TO with an additional feature, POC compliance. The present study aimed to evaluate prognostic impact of thus defined textbook oncological outcome (TOO) among patients undergoing gastrectomy for advanced GC. Patients and methods We collected data from a prospectively maintained database of all patients operated for GC between 2010 and 2020 in our institution. Patients with histologically confirmed and resectable advanced GC but without distant metastases, in whom multimodal treatment was planned by institutional MDT were included. Results A total of 194 patients were analyzed. In the multivariate analysis, patients with TOO had a 50 % lower risk of death than patients without TOO (medians: NR vs 42 months; HR = 0.50, p = 0.0109). Patients treated with POC had a 43 % lower risk of death than patients treated with only preoperative chemotherapy (medians: 78 vs 33 months; HR = 0.57, p = 0.0450). Patients with a pathological response (PR) in the primary tumor had a 59 % lower risk of death than patients without PR (medians: NR vs 36 months; HR = 0.41, p = 0.0229). POC combined with TO surgery significantly decreased the risk of death in advanced GC patients (medians: NR vs 42 months; HR = 0.35, p = 0.0258). Conclusion Since TOO is associated with improved survival, it may serve as a multimodal treatment quality parameter in patients with advanced GC.